@article{oai:repo.qst.go.jp:00049056,
 author = {Gen Matsumoto and Matsumoto, Kazuki and Kimura, Taeko and Suhara, Tetsuya and Higuchi, Makoto and Sahara, Naruhiko and Mori, Nozomu and Kimura, Taeko and Suhara, Tetsuya and Higuchi, Makoto and Sahara, Naruhiko},
 issue = {5},
 journal = {International Journal of Molecular Sciences},
 month = {May},
 note = {Neurofibrillary tangles composed of hyperphosphorylated tau protein are primarily
neuropathological features of a number of neurodegenerative diseases collectively termed tauopathy.
To understand the mechanisms underlying the cause of tauopathy, precise cellular and animal models
are required. Recent data suggest that the transient introduction of exogenous tau can accelerate the
development of tauopathy in the brains of non-transgenic and transgenic mice expressing wild-type
human tau. However, the transmission mechanism leading to tauopathy is not fully understood.
In this study, we developed cultured-cell models of tauopathy representing a human tauopathy.
Neuro2a (N2a) cells containing propagative tau filaments were generated by introducing purified tau
fibrils. These cell lines expressed full-length (2N4R) human tau and the green fluorescent protein
(GFP)-fused repeat domain of tau with P301L mutation. Immunocytochemistry and super-resolution
microscopic imaging revealed that tau inclusions exhibited filamentous morphology and were
composed of both full-length and repeat domain fragment tau. Live-cell imaging analysis revealed
that filamentous tau inclusions are transmitted to daughter cells, resulting in yeast-prion-like
propagation. By a standard method of tau preparation, both full-length tau and repeat domain
fragments were recovered in sarkosyl insoluble fraction. Hyperphosphorylation of full-length tau
was confirmed by the immunoreactivity of phospho-Tau antibodies and mobility shifts by sodium
dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). These properties were similar to
the biochemical features of P301L mutated human tau in a mouse model of tauopathy. In addition,
filamentous tau aggregates in cells barely co-localized with ubiquitins, suggesting that most tau
aggregates were excluded from protein degradation systems, and thus propagated to daughter cells.
The present cellular model of tauopathy will provide an advantage for dissecting the mechanisms of
tau aggregation and degradation and be a powerful tool for drug screening to prevent tauopathy},
 title = {Tau Fibril Formation in Cultured Cells Compatible with a Mouse Model of Tauopathy},
 volume = {19},
 year = {2018}
}